Rating scales were developed for quantification of locomotor activity, stereotyped behaviors and ataxia produced when PCP is administered to rats. PCP (0-15mg/kg, i.pp)-induced locomotion approximated an inverted U-shaped function for 30 min after administration but between 60-90 min locomotion was linearly related to dose. Stereotypies and ataxia were each linearly related to the dose of PCP administered throughout the 90 min rating period. Administration of PCP to unilateral substantia nigra 6-OHDA lesioned rats produced dose-dependent ipsilateral rotation, an effect which was antagonized by alpha-methyl-paratyrosine (AMPT). Pretreatment with butyrophenone neuroleptics produced dose-related antagonism of the behavioral effects of PCP. Phenothiazine neuroleptics, however, were generally ineffective PCP antagonists and actually increased PCP ataxia. Atropine sulfate enhanced PCP locomotion and stereotypies whereas physostigmine potentiated ataxia but had little effect on the other PCP behaviors. Methylphenidate stereotypies and PC-induced locomotion and stereotypies were antagonized by reserpine at a dose which enhanced amphetamine stereotypies. PCP increased amphetamine locomotion in reserpine- or vehicle-pretreated rats. Baclofen significantly antagonized the behavioral effects of PCP but other drugs with GABA agonist properties, diazepam and muscimol, increased PCP ataxia. Alpha-Adrenergic (phenoxybenzamine) and 5-HT antagonists (Cinnanserin, cyproheptadine) also primarily affected an increase in PCP ataxia. Withdrawal from chronic administration of haloperidol resulted in enhancement of the locomotion and ataxia produced by PCP. Naloxone had no effect on PCP behaviors while lithium carbonate potentiated PCP stereotypies and ataxia. In neurochemical studies we found that PCP or haloperidol alone had no effect on striatal DA content but that combined administration of these two drugs produced a significant decrease in striatal DA at 90 min. DA metabolites DOPAC and HVA were also elevated by PCP in haloperidol treated rats. Administration of PCP to rats pretreated with a low dose of haloperiodol accelerated the AMPT-induced depletion of DA.